The need for topical skin protectants (TSP) to protect soldiers from the threat of dermal exposure to chemical warfare agents (CWAs) arose during World War I. During World War II several nations developed and distributed TSPs, in the United States, M-5 ointment, a petroleum-based oil containing chloramine B, which reacts with and neutralizes sulfur mustard. Although M-5 is efficacious, its oily consistency makes it difficult to keep it in place and its user acceptability has not been good. In addition, extended use of M-5 has caused a high incidence of skin irritation.
TSPs require an inert material which can be applied on the skin in a thin layer to form an antipenetrant barrier to all known CWAs or other contact irritants and will not interfere excessively with normal skin functions. Improved TSPs are needed for protecting military personnel and civilians from percutaneous exposure to CWAs and protecting the skin from contact dermatitis arising from other sources as well.
A preferred TSP affords protection against CWAs and other toxic or irritating materials in all of the forms in which they might be encountered-liquid, aerosolized liquid and vapor. For example, perhaps the best-known vesicant CWA is 2,2'-dichlorodiethylsulfide (also known as "HD" or "sulfur mustard"), which was first used during World War I and is believed to have been used in during the recent Afghan and Iran/Iraq conflicts. It appears that only a small minority (about 1%) of the injuries caused by HD have been the result of direct liquid contact and only about 22% by indirect contact with liquid. The remainder of casualties has been attributed to HD vapor and/or aerosolized liquid.
In recent years a polyethylene glycol, PEG 540, has been considered for use as a TSP by the United States Army. PEG 540 is a proprietary blend of polyethylene glycol having a nominal molecular weight of 400 with a polyethylene glycol having a nominal molecular weight of 1450 to form a mixture of nominal 540 average molecular weight. PEG 540 is opaque to white in color and has the consistency of a soft waxy salve. PEG 540 has been used by the U.S. Army as a standard for screening the performance of candidate TSPs.
The Canadian military has developed barrier creams for use as TSPs. One product, hereinafter referred to as "Canadian Protective Cream", contains the strong nucleophile potassium 2,3-butanedione monoximate as an agent-degrading ingredient in a 1:1 mixture of polyethylene glycol monomethyl ethers MPEG 550 and MPEG 1900. Another preparation, hereinafter referred to as "Canadian Skin Cleanser", contains the same active ingredient in MPEG 550.
A variety of products have been offered commercially in civilian markets for use as protectant barriers. Among these are Barrier Biocream (Biomedic, Busnago, Italy) and Mane Street Barrier Creme (Mane Street Products Minneapolis, Minn.) both of which contain small amounts of a perfluorinated polyether; Biocontrol (Biocontrol, Coon Rapids, Minn.), which contains a modified-cellulose-based polymer; Multi Shield Skin Cream (Interpro, Haverhill, Mass.), which contains TEA-stearate in a mixture of monoethanolamine stearic acid amide, ethoxydiglycol, diethylene glycol monoethyl ether and acetic acid in water; pr88 Wash-off Hand Protection Cream (Ursula Rath GmbH, Senden, Germany), which contains glycerine in an aqueous mixture of sodium silicate, soap, emulsifier, wax and fragrance; pr99 Skin Protection Lotion (Ursula Rath), which contains PEG 300 glyceryl oleate in an aqueous mixture of cetearyl octanoate, microcrystalline wax, mineral oil, lanolin, dimethicone, tocopheryl acetate, glycerin, magnesium sulfate, phenoxy ethanol and fragrance; pr2000 Skin Care Lotion (Ursula Rath), which contains stearyl alcohol in a mixture of stearyth-7, stearyth-10, ceteareth-25, cetearyl octanoate, cetearyl alcohol, glyceryl stearate, mineral oil, dimethicone, tocopheryl nicotinate, bisabolol, glyceryl linoleate, glyceryl linolenate, panthenol, propylene glycol, phenoxy ethanol, carbomer, tetrahydroxypropyl ethylene diamine and fragrance; and Ivy Block (United Catalysts, Louisville, Ky.), which contains cyclomethicone, quaternium-18 bentonite and SD alcohol. Investigation of these materials has shown that they do not afford satisfactory protection against CWAs.
Recent work has shown that certain perfluorinated greases used as lubricants for extreme operating conditions show good protection against contact with organophosphates and protection against vesicants such as HD (Snider et al., "An in vitro Cultured Skin Penetration Model for Evaluating the Efficacies of Topical Skin Protectants Against Anticholinesterase Compounds", Abstract #341, 1994 Annual Meeting of the Society of Toxicology; McCreery et al., "Formulation Optimization for Perfluorinated Topical Skin Protectants (TSPs)", Abstract, U.S. Army Medical Research and Development Command 1993 Medical Defense Bioscience Review Proceedings May 10-13, 1993 Proceedings, Vol. 1, pp 293-4). The materials described in those publications are quite expensive but they have been used commercially as specialty greases because they provide good lubricity and they are chemically inert and stable at high temperatures. These greases are blends of finely divided polytetrafluoroethylene (PTFE) in perfluorinated polyether base oils. A typical commercially available grease contains about 15-30% PTFE dispersed in a perfluorinated polyether base oil having a viscosity of 800 cSt (20.degree. C.) or more. Certain commercial greases have been found to afford protection against liquid CWAs both in vitro and in vivo. One such material was Fomblin.RTM. RT15, a mixture of 28-30% (w/w) Algoflon.RTM. L206 PTFE in Fomblin.RTM. YR oil sold by Ausimont, USA as an industrial grease. Other perfluorinated greases are sold by Du Pont under the Krytox.RTM. trade name. These include Krytox.RTM. LVP, a high vacuum grease containing about 30% by weight PTFE in Krytox.RTM. 16256 vacuum pump fluid; Krytox.RTM. 240AC, a mixture of about 13-16% VYDAX.RTM. 1000 in Krytox.RTM. 143AC perfluorinated oil; and Krytox.RTM. 340AC, a mixture of about 28% PTFE in Krytox.RTM. 143AC perfluorinated oil. These commercial materials have similar compositions and characteristics. All are simple mixtures of a perfluorinated polyether base oil having a viscosity of 800-2700 cSt (20.degree. C.) or more thickened with fine polytetrafluoroethylene (PTFE) particulates. Although the compositions afford good TSP properties they are quite sticky, as would be expected for materials used as greases. Experience has shown that sticky topical products are not acceptable to users. Furthermore they may cause debris and foreign bodies to become lodged in the barrier as well, compromising its TSP qualities. In addition, perfluorinated polyethers are costly, which probably would be a practical limitation to their use in high concentrations or over long periods of time. In short, although they form effective protective barriers when applied to the skin, the commercial grease products are sufficiently sticky and expensive to make it problematical that they would be suitable as TSPs.
The basic repeating units of the base oils used in the commercial grease products differ somewhat, but both are almost totally perfluorinated, have multiple ether linkages in their mainly unbranched chains, and have average molecular weights in the range of 5,000 to 7,000. They are nearly inert chemically, do not freeze at -196 .degree. C. or boil at 280 .degree. C.; have relatively high viscosities (800-2700 cSt or more); have no odor or taste; have very low vapor pressures; and very low solubility in nearly all solvents.
The PTFE particulates used as thickeners in the commercial grease products are also similar. The particles are generally spherical in shape and have sizes ranging from 0.1 .mu. to 10 .mu. or more, but most have sizes in which &gt;90% of the particles fall between 3 and 5 .mu. in size. Since their surfaces are corrugated with deep crevices, the particles possess a high surface area, up to about 15 M.sup.2 /g. The polymers are high molecular weight, averaging about 200,000. The structure and size make the polymers nearly chemically inert, except in strong acid.
Perfluorinated polyether base oils are typically synthesized by a chain reaction starting from perfluoroethylene or perfluoropropylene oxides. The reaction produces a distribution of molecular weights (MW) or polymer number (n) that is normally gaussian, but can be skewed to higher or lower MWs by reaction conditions. The crude products may be used directly but usually are fractioned by vacuum molecular distillation into "cuts", similar to those used as petroleum products. Each cut has an average boiling point and a boiling point range that define the molecular weight distribution. The viscosity, boiling point, vapor pressure, and other physical parameters of the oils vary proportionately with the chain length or polymer number. Some commercial products are produced by blending higher- and lower-viscosity (molecular weight) materials to obtain a desired viscosity.
Brunetta et al., U.S. Pat. No. 4,803,067, describes the use of minor amounts of perfluorinated polyether oils as ingredients of oil/water or water/oil emulsions used in formulating compositions stated to be useful as cosmetics, waterproof sunscreens, carriers for drugs and as protective and barrier creams. Pereira, U.S. Pat. No. 4,981,841, discloses water-in-oil emulsions stated to be useful as topical treatments for skin and hair which contain "skin benefit ingredients". Perfluorinated polyether oils are listed among the many possible materials to be included in minor amounts as "skin benefit ingredients". Pantini et al., U.S. Pat. No. 5,092,023, desribes cosmetic cleaning emulsions which contain minor amounts of perfluorinated polyethers among other ingredients. Oliver, French Patent Application 2,664,162, describes emulsions stated to be useful as barrier coatings which contain minor amounts of a perfluorinated polyether among other ingredients.
Maillat, U.S. Pat. No. 4,937,010, describes non-aqueous paint formulations which contain, inter alia, perfluorinated polyether oils which act as immiscible lubricating ingredients in the coatings. Some of the commercial coatings used Maillat's examples contain unstated amounts of polytetrafluoroethylene (PTFE) powder.
Trussler et al., UK Patent Application 2,244,601A, describes a conductive layer for circuit boards which contains a perfluorinated grease or gel such as Fomblin ZLHT.